1. Technical Field of the Invention
The invention relates, as novel and useful industrial products, to biarornatic compounds which are activators of receptors of the Peroxisome Proliferator-Activated Receptor type of subtype γ (PPARγ). It also relates to their method of preparation and to their use in pharmaceutical compositions for use in human or veterinary medicine, or alternatively in cosmetic compositions.
2. Description of the Prior Art
The activity of the PPAR-type receptors has been the subject of numerous studies. There may be mentioned, as a guide, the publication entitled “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol 111, 1998, p. 1116–1121, in which a large number of bibliographic references relating to PPAR-type receptors is listed. There may also be mentioned, as a guide, the dossier entitled “The PPARs: From orphan receptors to Drug Discovery”, Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach, and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, p. 527–550.
The PPAR receptors activate transcription by binding to elements of DNA sequences, called peroxisome proliferator response elements (PPRE), in the form of a heterodimer with the retinoid X receptors (called RXRs).
Three human PPAR subtypes have been identified and described: PPARα, PPARγ and PPARδ (or NUC1).
PPARα is mainly expressed in the liver while PPARδ is ubiquitous.
PPARγ is the most widely studied of the three subtypes. All the references suggest a critical role of the PPARγ receptors in the regulation of differentiation of adipocytes, where it is highly expressed. It also plays a key role in systemic lipid homeostasis.
It has in particular been described in Patent Application WO 96/33724 that PPARγ-selective compounds, such as prostaglandin-J2 or -D2, are potential active agents for treating obesity and diabetes.
Moreover, the applicant has already described in Patent Application FR98/02894 the use of PPARγ-activating compounds in the preparation of a pharmaceutical composition, the composition being intended for treating skin disorders linked to an abnormality of differentiation of epidermal cells.